Phytomedicine最新文献

{"title":"Corrigendum to \"KAJF alleviated colorectal cancer liver metastasis by reshaping the gut microbiota and inhibiting M2-like macrophage polarization\" [Phytomedicine, 142(2025) 156766].","authors":"Zongmei Zheng, Yizhao Du, Hua Jiang, Zhenpeng Shi, Hailun Zhou, Lijing Jiao, Peifeng Liu, Yabin Gong","doi":"10.1016/j.phymed.2025.156848","DOIUrl":"10.1016/j.phymed.2025.156848","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":" ","pages":"156848"},"PeriodicalIF":6.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppressing ferroptosis via modulating FTH1 by silybin for treatment of renal fibrosis","authors":"Jia-Qin Hu ,&nbsp;Cang-Qiong Ning ,&nbsp;Fang-Cao Pi ,&nbsp;Xue-Ni Cai ,&nbsp;Jian Zhou ,&nbsp;Nan Wang ,&nbsp;Li-Li Yu ,&nbsp;Hua Zhou ,&nbsp;Ying Xie","doi":"10.1016/j.phymed.2025.156937","DOIUrl":"10.1016/j.phymed.2025.156937","url":null,"abstract":"<div><h3>Background</h3><div>Renal fibrosis, a hallmark pathological manifestation of chronic kidney disease, arises from diverse etiological factors. While ferroptosis has emerged as a pivotal contributor to renal fibrogenesis, the regulatory mechanisms governing this process—particularly those involving iron metabolism—remain poorly characterized.</div></div><div><h3>Objective</h3><div>This study aimed to elucidate the molecular mechanism through which silybin modulates FTH1 to regulate iron homeostasis, thereby suppressing ferroptosis and attenuating fibrotic progression in renal pathology.</div></div><div><h3>Study Design</h3><div>The therapeutic efficacy of ferrostatin-1 (Fer-1) and silybin was systematically evaluated in complementary in vivo and in vitro renal fibrosis models. Mechanistic investigations employed FTH1 knockout and overexpression systems to validate its role as a therapeutic target.</div></div><div><h3>Methods</h3><div>Fibrotic inhibition was assessed histologically and via quantification of fibrotic markers. Iron ion concentrations and reactive oxygen species (ROS) levels were measured using standardized commercial assay kits. The silybin-FTH1 interaction was investigated through surface plasmon resonance (SPR) analysis.</div></div><div><h3>Results</h3><div>Silybin administration demonstrated potent ferroptosis inhibition, significantly ameliorating pathological alterations and fibrotic marker expression across experimental models. FTH1 ablation exacerbated ferroptotic cell death and fibrotic progression, whereas FTH1 overexpression conferred robust protection against renal fibrosis. Mechanistically, silybin directly bound FTH1 protein, stabilizing its expression to counteract iron overload-induced ferroptosis.</div></div><div><h3>Conclusions</h3><div>Our study unveils FTH1 stabilization as a mechanistically novel strategy to disrupt the vicious cycle of iron overload and ferroptosis in renal fibrosis, offering a superior alternative to conventional ferroptosis inhibitors targeting downstream effectors.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156937"},"PeriodicalIF":6.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bufalin enhanced temozolomide efficacy by promoting EGFR protein degradation in glioblastoma","authors":"Runze Yu ,&nbsp;Yuhan Li ,&nbsp;Bo Wang ,&nbsp;Yuxuan Guo ,&nbsp;Yixi Sun ,&nbsp;Yingjie He ,&nbsp;Jianhua Xiong ,&nbsp;Shulong Jiang ,&nbsp;Lei Han","doi":"10.1016/j.phymed.2025.156987","DOIUrl":"10.1016/j.phymed.2025.156987","url":null,"abstract":"<div><h3>Background</h3><div>Glioblastoma (GBM), the most aggressive form of glioma, is associated with a poor patient prognosis. Temozolomide (TMZ), the first-line chemotherapeutic agent for GBM patients, has its efficacy closely tied to patient prognosis. The epidermal growth factor receptor (EGFR) can affect TMZ efficacy by activating its downstream pathways.</div></div><div><h3>Purpose</h3><div>This research aimed to explore the potential mechanism of bufalin as a therapeutic agent for GBM.</div></div><div><h3>Methods</h3><div>The pharmacological mechanism was predicted using network pharmacology, molecular docking, and molecular dynamics simulation, and subsequently validated through <em>in vivo</em> and <em>in vitro</em> studies.</div></div><div><h3>Result</h3><div>This study found that bufalin, a traditional Chinese medicine, may interact with EGFR and modulate GBM progression. Western blot and immunofluorescence demonstrated that bufalin promoted the EGFR protein degradation through the chaperone-mediated autophagy (CMA). TUNEL, γH₂AX immunofluorescence, and comet assays verified the impact of bufalin on enhancing the efficacy of TMZ in GBM. In a tumor xenograft model, the combination of TMZ and bufalin showed significantly greater efficacy than either agent alone.</div></div><div><h3>Conclusion</h3><div>Bufalin significantly reduced EGFR protein levels via CMA and enhanced TMZ efficacy in GBM by modulating the EGFR signaling pathway. Pharmacological and molecular biological experimental data indicated that bufalin has great potential as a new drug to enhance the efficacy of TMZ in GBM in the future.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156987"},"PeriodicalIF":6.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated analysis of metabolomics, network pharmacology, and intestinal microbiota reveals Tibetan herb E’se ameliorate disorders of glycolipid metabolism in db/db mice","authors":"Luyao Zheng ,&nbsp;Li Liu ,&nbsp;Shangxiao An ,&nbsp;Xue Chen ,&nbsp;Hua Hua ,&nbsp;Junning Zhao","doi":"10.1016/j.phymed.2025.156979","DOIUrl":"10.1016/j.phymed.2025.156979","url":null,"abstract":"<div><h3>Background</h3><div>E’se (<em>Malus toringoides (Rehd.) Hughes or Malus transitoria (Batal.) Schneid</em>) is widely used as a drug for the treatment of diabetes mellitus in China, but the mechanism by which E 'se regulates disorders of glucose-lipid metabolism has lacked in-depth study. The intestinal microbiota also plays a crucial role in lipid metabolism, but whether E 'se regulates this process by modulating the intestinal microbiota needs to be further investigated.</div></div><div><h3>Objective</h3><div>Effects of aqueous extract of E'se decoction lyophilized powder (EMT) on metabolic disorders of glucose and lipid, and its mechanism of glucose regulation mediated through intestinal microbiota in db/db mice.</div></div><div><h3>Methods</h3><div>UPLC-Q-TOF-MS was used to analyze the chemical composition of EMT and predict potential therapeutic targets in combination with network pharmacology and molecular docking. The pharmacological effects of EMT were evaluated in six groups of db/db mice (db/db group, rosiglitazone group, low, medium, and high dose EMT of 0.75 g, 1.5 g, 3.0 g/kg/d) and db/m (WT) for 4 weeks’ treatment. ELISA was performed to determine serum concentrations of glycated hemoglobin (HbA1C), glycated serum protein (GSP), free fatty acids (FFA), fasting insulin (FINS), lipopolysaccharide (LPS), and glucagon-like peptide-1 (GLP-1), feces was used for microbial 16S rRNA sequencing and short-chain fatty acid (SCFA) quantification, and organs were used for pathologic assessment and subsequent mechanistic studies.</div></div><div><h3>Results</h3><div>Based on network pharmacology and molecular docking predictions, the role of EMT in regulating glycolipid metabolism mainly involves pathways such as G protein-coupled receptor(GPR) activity and GLP-1 secretion. Subsequently, it was demonstrated in animal experiments that EMT significantly ameliorated the abnormalities of glycolipid metabolism in db/db mice. Further microbial 16S r RNA sequencing analysis revealed significant changes in the composition of the intestinal microbiota, with increased abundance of <em>Muribaculacea, Alloprevotella, Rikenella,</em> and <em>Parabacteroides</em>, associated with enhanced SCFA secretion. Increased SCFA activated hepatic GPR, promoted GLP-1 secretion, modulated secretion of inflammatory factors and oxidative factors in the intestine, and down-regulated the NF-κB pathway in db/db mice.</div></div><div><h3>Conclusion</h3><div>Studies have demonstrated that E'se can effectively alleviate abnormalities of glucose-lipid metabolism and intestinal barrier inflammation, making it a novel drug with great therapeutic potential.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156979"},"PeriodicalIF":6.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tanshinone IIA modulates Sirt5 and Metll3 interaction to govern mitochondria-endoplasmic reticulum unfolded protein response in coronary microvascular injury","authors":"Xiangyi Pu ,&nbsp;Qiaomin Wu ,&nbsp;Zhaoqi Yan ,&nbsp;Siyuan Zhou,&nbsp;Qin Zhang,&nbsp;Xinai Zhang,&nbsp;Yongyuan Cai,&nbsp;Zhiming Liu,&nbsp;Ruxiu Liu,&nbsp;Xing Chang","doi":"10.1016/j.phymed.2025.156982","DOIUrl":"10.1016/j.phymed.2025.156982","url":null,"abstract":"<div><h3>Background</h3><div>Traditional Chinese medicine (TCM) has demonstrated significant advantages in the treatment of coronary microvascular injury, offering novel therapeutic strategies for cardiovascular diseases. Among its active compounds, Tanshinone IIA (TS) has been shown to regulate mitochondrial and endoplasmic reticulum (ER) function. However, the precise mechanisms through which TS exerts its effects, particularly via METTL3- and SIRT5-mediated unfolded protein response (UPR) pathways in microvascular endothelial cells (MECs), remain poorly understood.</div></div><div><h3>Purpose</h3><div>This study aims to elucidate the role of SIRT5 and METTL3 in mediating the protective effects of TS on mitochondrial and ER function in MECs, focusing on the UPR pathways.</div></div><div><h3>Study design</h3><div>Cardiomyocyte-specific knockout and transgenic mice were utilized to investigate the role of SIRT5 and METTL3. MECs from experimental groups were treated with TS, and various cellular functions were analyzed.</div></div><div><h3>Methods</h3><div>The study employed confocal microscopy, electron microscopy, JC-1 assay, MTT assay, and molecular docking techniques to assess mitochondrial and ER functions. Key markers, including mitochondrial membrane potential, protein expression (PINK1, Parkin, PERK, CHOP, and Nrf-1), and transcription levels (PGC1-α, TFAM, and ATF5), were quantified. Calcium ion levels and mitochondrial respiratory functions were also evaluated.</div></div><div><h3>Results</h3><div>TS treatment enhanced mitochondrial stability, restored mitochondrial membrane potential, and regulated calcium overload through METTL3- and SIRT5-mediated UPR pathways. It upregulated protective proteins (PGC1-α, TFAM, and Nrf-1) while reducing oxidative stress and ER stress markers (CHOP, PERK, and ATF5). Molecular docking confirmed a direct interaction between SIRT5 and METTL3. These changes collectively mitigated microvascular endothelial damage and normalized mitochondrial biogenesis.</div></div><div><h3>Conclusion</h3><div>TS exerts protective effects on MECs by stabilizing mitochondrial function, alleviating calcium overload, and modulating UPR signaling via METTL3 and SIRT5.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156982"},"PeriodicalIF":6.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shen-Ying-Yang-Zhen formula promotes angiogenesis around hair follicles, alleviates oxidative stress, and inhibits hair follicle apoptosis through the VEGF/Akt/Caspase-9 signaling axis","authors":"Huixing Zhang ,&nbsp;Lin Su ,&nbsp;Yan Qiang ,&nbsp;Junnan Chen ,&nbsp;Shiyu Hang ,&nbsp;Mingxi Liu ,&nbsp;Han Ding ,&nbsp;Qianxi Ouyang ,&nbsp;Yangzhuangzhuang Zhu ,&nbsp;Xiaoyu Wang ,&nbsp;Xiaowen Zhu ,&nbsp;Qiuyue Wang ,&nbsp;Wuqing Wang ,&nbsp;Zihang Xu ,&nbsp;Chunpu Zou","doi":"10.1016/j.phymed.2025.156963","DOIUrl":"10.1016/j.phymed.2025.156963","url":null,"abstract":"<div><h3>Background</h3><div>Androgenic alopecia (AGA) represents the most predominant form of hair loss in clinical practice, yet currently approved pharmacological options (e.g., finasteride and minoxidil) face limitations in safety and long-term efficacy. Shen-Ying-Yang-Zhen formula (SYF) is a classical prescription in traditional Chinese medicine to AGA; nevertheless, its specific mechanisms of action in addressing AGA remain to be further explored and elucidated. In our study, we for the first time propose that SYF uniquely reshapes the perifollicular microenvironment through dual regulation of oxidative stress and angiogenesis, thus providing a potential medication for AGA.</div></div><div><h3>Methods</h3><div>In this study, the chemical constituents of SYF were identified using UPLC-MS. An AGA mouse model was established by induction with testosterone propionate (TP), and a human dermal papilla cell (HDPC) model was induced by dihydrotestosterone (DHT). The mechanism underlying SYF treatment for AGA was examined by merging network pharmacology with RNA sequencing, and the findings were corroborated through flow cytometry, multiple immunofluorescences, Western blotting, RT-qPCR, and ELISA techniques.</div></div><div><h3>Results</h3><div>In the AGA mouse model, histological analysis revealed that oral administration of SYF significantly increased skin thickness and hair follicle density (2.8-fold vs. TP group, <em>p</em> &lt; 0.001). Immunofluorescence staining further confirmed that SYF treatment promoted a 2.9-fold increase in p-S6-positive hair follicles—indicative of anagen-phase induction (<em>p</em> &lt; 0.001). Network pharmacology and RNA-seq analyses showed that SYF treatment was associated with cellular oxidative stress and the angiogenic microenvironment around AGA hair follicles, which may be related to targets such as VEGF and Akt Additionally, expression of Ki67, SRY-box transcription factor 9, phospho-S6 ribosomal protein (p-S6), and Nrf2 was enhanced in the skin of the SYF-treated mice, whereas reactive oxygen species expression was decreased. RT-qPCR analysis revealed downregulation of follicle degradation-related factors DKK1, IL-6, and TGFβ1, along with decreased Caspase-9 expression and upregulated key targets VEGF and Akt in the VEGF/Akt/Caspase-9 signaling axis. In the DHT-HDPC model, SYF promoted the proliferation of HDPCs and elevated the Bcl-2/Bax ratio, which in turn suppressed apoptosis of HDPCs in vitro.</div></div><div><h3>Conclusion</h3><div>SYF shows promise as a therapeutic agent for prevention of hair loss by improving oxidative stress and angiogenesis in the area surrounding hair follicles in AGA. It reduces apoptosis in DHT-treated HDPCs by regulating the VEGF/Akt/Caspase-9 signaling axis. This multi-target, systems-level approach highlights SYF’s potential as a novel therapeutic agent for AGA.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156963"},"PeriodicalIF":6.7,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Raspberry ketone alleviates radiation-induced lung injury through the STAT2-P2X7r/NLRP3 signaling pathway","authors":"Yu-Chen Jiang ,&nbsp;Bin Zhao ,&nbsp;Peng Jiang ,&nbsp;Si-Ying Wang ,&nbsp;Lin Ma ,&nbsp;Guo-Li Wu ,&nbsp;Man-Li Wang ,&nbsp;Hai-Ming Sun","doi":"10.1016/j.phymed.2025.156984","DOIUrl":"10.1016/j.phymed.2025.156984","url":null,"abstract":"<div><h3>Background</h3><div>Radiation-induced lung injury (RILI) is a frequent side effect in patients with breast cancer receiving radiotherapy. Currently, there is no optimal radioprotective agent that is widely utilized for RILI treatment. Raspberry ketone (RK) is a natural aromatic compound found in raspberries (Rubus idaeus L.). A recent study by our research revealed that RK has strong anti-inflammatory and anti-fibrosis effects. However, its actual mechanism of action in inflammation-related lung injury remains elusive.</div></div><div><h3>Purpose</h3><div>This study aimed to clarify whether RK can alleviate RILI and determine the possible underlying mechanisms. C57BL/6 mice were exposed to Coγ-rays to establish a lung injury model. RK was orally administered to the mice daily for 14 days, followed by STAT2 gene silencing. Lung tissue, serum, and bronchoalveolar lavage fluid were collected to detect lung injury-related biomarkers. Tissue morphological changes and biomarker expression related to the ECM, inflammation, EMT, and pyroptosis in the lung tissue were detected.</div></div><div><h3>Methods</h3><div>C57BL/6 mice were exposed to Coγ-rays to establish a lung injury model. RK was orally administered to the mice daily for 14 days, followed by STAT2 gene silencing. Primary lung fibroblasts were activated with TGF-β or supernatant under inflammatory conditions and incubated with RK or Nifuroxazide, respectively. BMDMs were also treated with LPS and RK to form a conditioned medium. Primary lung fibroblasts and BMDMs were injected with siRNA-STAT2.</div></div><div><h3>Results</h3><div>RK could improve the levels of biochemical indicators in the lung tissue, suppress the expression of ECM markers, and downregulate the levels of inflammatory factors, such as IL-1β, in RILI. RK could also regulate radiation-induced histopathological damage and EMT progression and inhibit the upregulation of pyroptosis-related proteins. Furthermore, RK inhibited the expression of the downstream signals of STAT2 and P2 × 7r. In addition, STAT2 deletion inhibited the occurrence of ECM, inflammation, EMT, and pyroptosis. Notably, silencing the STAT2 gene led to a low expression of P2 × 7r and the NLRP3 inflammasome in the lung tissue of RILI mice, primary lung fibroblasts, and BMDMs. Primary lung fibroblasts were activated with conditioned medium from LPS-primed BMDMs, which resulted in significant enhance of EMT markers and inflammatory cytokines.</div></div><div><h3>Conclusion</h3><div>This study indicated that RK improved RILI through STAT2-P2 × 7r/NLRP3 signaling. RK might be a prospective therapeutic candidate, and its mechanism would be a novel approach for RILI treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156984"},"PeriodicalIF":6.7,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of heart-on-a-chip and metabolomics for understanding the toxicity-attenuating effect of ethnomedicinal processing","authors":"Xinmei Xu ,&nbsp;Yue Liu ,&nbsp;Shufu Yu ,&nbsp;Suet Cheung ,&nbsp;Mengyang Cui ,&nbsp;Yongjian Ai ,&nbsp;Yi Zhang ,&nbsp;Qionglin Liang","doi":"10.1016/j.phymed.2025.156985","DOIUrl":"10.1016/j.phymed.2025.156985","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Tiebangchui (TBC), is a well-known traditional Tibetan medicine that coexists with toxicity and effects. Highland barley wine is an effective and unique processing method to reduce TBC’s toxic side effects. However, the toxicity reduction mechanism is ambiguous and needs to be explored urgently. Meanwhile, the limitations of traditional animal models and two-dimensional (2D) cell culture models urgently require the development of more reliable analytical platforms for drug detection.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study design&lt;/h3&gt;&lt;div&gt;The integrated metabolomics and biomimetic 3D anisotropic heart-on-a-chip were utilized to reveal the toxicity-attenuating effect of highland barley wine-processed TBC from the dual perspectives of &lt;em&gt;in vitro&lt;/em&gt; compositional changes and &lt;em&gt;in vivo&lt;/em&gt; toxicity mechanisms. The combination of organ-on-a-chip and metabolomics provides a powerful tool for achieving spatiotemporal control of cell growth and biochemistry, as well as rapid detection of small molecule metabolites.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) coupled with global natural products social molecular networking (GNPS) was utilized for the expeditious identification of chemical constituents in both raw and processed TBC products. Multivariate statistical analysis was applied to screen for differential constituents before and after processing, followed by quantification of these constituents using ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS). After constructing a 3D heart-on-a-chip model, the structure and function of the chip model were validated via COMSOL finite element analysis, immunofluorescence, and qPCR. Leveraging this chip model, integrating molecular biology and metabolomics was employed to further elucidate the detoxification mechanism by highland barley wine-processed TBC.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The comprehensive analytical strategies demonstrated that the loss of the toxic constituents of TBC through leaching during steeping and the esterification of diterpene alkaloids with long-chain fatty acids in highland barley wine to produce less toxic lipid alkaloids were the main mechanisms of toxicity reduction. Furthermore, a biomimetic 3D anisotropic heart-on-a-chip was fabricated to evaluate differences in cardiotoxicity before and after processing. The results illustrated that the raw TBC and aconitine caused a significant increase in the extracellular LDH level, resulting in intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; overload, substantial ROS production, and metabolite disorders primarily associated with the tricarboxylic acid cycle. This cascade of reactions ultimately led to apoptosis; however, highland barley wine processing of TBC mitigated these cardiotoxic effects.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This work not only revealed the toxicity-reducing mechan","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156985"},"PeriodicalIF":6.7,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tanshinone IIA attenuates sepsis-induced lung injury by reducing VEGFR2/PI3K/AKT-driven mitochondrial disruption dependent apoptosis","authors":"Delida Aidebaike ,&nbsp;Hailong Gong ,&nbsp;Yun Xia ,&nbsp;Guoqing Jing ,&nbsp;Huifan Liu ,&nbsp;Huimin Zhou ,&nbsp;Die Wu ,&nbsp;Jing Zuo ,&nbsp;Cheng Yang ,&nbsp;Xing Wang ,&nbsp;Yingyue Dong ,&nbsp;Jie Yan ,&nbsp;Xue Chen ,&nbsp;Zihan Lei ,&nbsp;Junjie Liang ,&nbsp;Xiaojing Wu ,&nbsp;Xuemin Song","doi":"10.1016/j.phymed.2025.156957","DOIUrl":"10.1016/j.phymed.2025.156957","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis-induced lung injury (SILI) is marked by excessive inflammation and apoptosis, posing considerable therapeutic problems owing to the scarcity of targeted therapy. Tanshinone IIA (TanIIA), a bioactive molecule extracted from <em>Salvia miltiorrhiza</em>, demonstrates potential in regulating inflammatory pathways and enhancing cellular resilience.</div></div><div><h3>Purpose</h3><div>This study comprehensively examined the therapeutic mechanisms of TanIIA in SILI by an integrated methodology that incorporates network pharmacology, molecular docking, and comprehensive experimental validation.</div></div><div><h3>Methods</h3><div>Network pharmacology and WGCNA analysis of GSE239388 revealed possible treatment targets for TanIIA. Computational analysis utilizing molecular docking techniques and molecular dynamics simulations validated a stable intermolecular connection between TanIIA and the vascular endothelial growth factor receptor 2.</div><div>TanIIA's therapeutic effectiveness was evaluated in vivo using septic mouse model. BEAS-2B cells treated with LPS in vitro were employed to elucidate the underlying mechanisms. Western blotting, qRT-PCR, immunohistochemistry, flow cytometry, and mitochondrial function assays were performed to evaluate gene expression, apoptosis, and mitochondrial functionality.</div></div><div><h3>Results</h3><div>VEGFR2 was identified as a critical therapeutic target of TanIIA in SILI. Treatment with TanIIA significantly enhanced survival rates, mitigated lung histopathological damage, and decreased levels of pro-inflammatory cytokines in CLP-induced septic mice. Mechanistically, TanIIA suppressed the VEGFR2-PI3K-AKT signaling pathway, preserving mitochondrial integrity and inhibiting apoptosis. Additional validation was obtained using LPS-treated BEAS-2B epithelial cells, reinforcing the initial findings.</div></div><div><h3>Conclusion</h3><div>TanIIA provides protective effects against SILI by specifically targeting VEGFR2 and inhibiting the PI3K/AKT signaling pathway, which helps maintain mitochondrial homeostasis and reduces apoptosis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156957"},"PeriodicalIF":6.7,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Geniposide via enema alleviates colitis by modulating intestinal flora and bile acid metabolites, inhibiting S100A8/S100A9/NF-κB, and promoting TGR5 inhibition of NLRP3 inflammasome” [Phytomedicine, 142 (2025), 156791]","authors":"Bao-xin Zheng ,&nbsp;Yan Yi ,&nbsp;Xing-wen Wang ,&nbsp;Chun-ying Li ,&nbsp;Yong Zhao ,&nbsp;Jing-zhuo Tian ,&nbsp;Lian-mei Wang ,&nbsp;Jia-yin Han ,&nbsp;Chen Pan ,&nbsp;Su-yan Liu ,&nbsp;Chen-yue Liu ,&nbsp;Sha-Sha Qin ,&nbsp;Xuan Tang ,&nbsp;Mei-ting Liu ,&nbsp;Ai-hua Liang","doi":"10.1016/j.phymed.2025.156934","DOIUrl":"10.1016/j.phymed.2025.156934","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"144 ","pages":"Article 156934"},"PeriodicalIF":6.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}